Animal models of human disease Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease

Swanborg, Robert H.

doi:10.1016/0090-1229(95)90130-2

Cited by 204 publications

(128 citation statements)

References 88 publications

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“…It is thought that initiation of MS is triggered by myelin-specific Th1 or Th17 cells, which in turn generate the expansion of resident microglia and infiltration of monocytes (32)(33)(34). The latter groups of cells appear crucial in determining the severity of the acute inflammatory phase of the disease.…”

Section: Discussionmentioning

confidence: 99%

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Denney

Kok

Cole

et al. 2012

The Journal of Immunology

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Neuropathology in multiple sclerosis is closely linked to presence of macrophages in the CNS. Both M1 (inflammatory) and M2 (alternatively activated, noninflammatory) macrophages are found in the inflamed CNS and thought to differentiate from infiltrating monocytes. It is unclear whether the balance of M1 and M2 macrophages can be altered and whether this affects disease outcome. We show in this article that Ly6Chi inflammatory monocytes are the early and dominant infiltrating cells in the CNS during experimental autoimmune encephalomyelitis, a model for the acute phase of multiple sclerosis. Activation of invariant NKT (iNKT) cells reduced the frequency of Ly6Chi monocytes and increased the proportion of M2 macrophages in the CNS with associated improvement in neurologic impairment. In contrast, iNKT-deficient mice showed higher numbers of Ly6Chi monocytes, reduced M2, and much more severe disease. Adoptive transfer of M2-enriched cells to iNKT-deficient mice markedly improved neurologic impairment. In vitro and in vivo experiments showed that iNKT cells promote differentiation of monocytes to M2 macrophages in an IL-4 and CD1d-dependent process. These findings indicate that infiltrating Ly6Chi inflammatory monocytes are early players in acute neuroinflammation and that their frequency and differentiation can be influenced by activation of iNKT cells with resultant improvement in disease outcome.

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Section: Discussionmentioning

confidence: 99%

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Denney

Kok

Cole

et al. 2012

The Journal of Immunology

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“…Draining lymph nodes and spleen from naive V␣2.3, V␤8.2 TCR-transgenic mice were cultured using different concentrations of MBPAc [1][2][3][4][5][6][7][8][9][10][11] in the presence of various concentrations of 15d-PGJ2. As shown in Fig.…”

Section: D-pgj2 Suppresses T Cell Proliferation and Cytokine Secretmentioning

confidence: 99%

“…When TCR Tg T cells specific for MBP Ac [1][2][3][4][5][6][7][8][9][10][11] were activated in vitro with Ag for 4 days in the presence or the absence of 15d-PGJ2 and subsequently transferred into naive B10.PL recipients, the presence of 15d-PGJ2 inhibited the encephalitogenicity and resulted in a delay in the onset and a decrease in the severity of disease (Fig. 5).…”

Section: D-pgj2 Inhibits the Encephalitogenic Potential Of Mbp-specmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-γ Agonist 15-Deoxy-Δ12,1412,14-Prostaglandin J2 Ameliorates Experimental Autoimmune Encephalomyelitis

Diab¹,

Deng²,

Smith³

et al. 2002

The Journal of Immunology

278

221

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Peroxisome proliferator-activated receptors (PPAR) are members of a nuclear hormone receptor superfamily that includes receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Previous studies dealing with PPAR-γ expression in the immune system have been limited. Recently, PPAR-γ was identified in monocyte/macrophage cells. In this study we examined the role of PPAR-γ in experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis. The hypothesis we are testing is whether PPAR-γ plays an important role in EAE pathogenesis and whether PPAR-γ ligands can inhibit the clinical expression of EAE. Initial studies have shown that the presence of the PPAR-γ ligand 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) inhibits the proliferation of Ag-specific T cells from the spleen of myelin basic protein Ac1–11 TCR-transgenic mice. 15d-PGJ2 suppressed IFN-γ, ΙL-10, and IL-4 production by both Con A- and myelin basic protein Ac1–11 peptide-stimulated lymphocytes as determined by ELISA and ELISPOT assay. Culture of encephalitogenic T cells with 15d-PGJ2 in the presence of Ag reduced the ability of these cells to adoptively transfer EAE. Examination of the target organ, the CNS, during the course of EAE revealed expression of PPAR-γ in the spinal cord inflammatory infiltrate. Administration of 15d-PGJ2 before and at the onset of clinical signs of EAE significantly reduced the severity of disease. These results suggest that PPAR-γ ligands may be a novel therapeutic agent for diseases such as multiple sclerosis.

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“…Inflammation is likely primarily mediated Ž . by T cells Swanborg, 1995 , but for demyelination the involvement of opsonizing antibodies and complement ap-Ž pears essential Linington and Lassmann, 1987;Linington . et al, 1992;Genain et al, 1995 .…”

Section: žmentioning

confidence: 99%

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

Laman

Meurs²,

Schellekens³

et al. 1998

Journal of Neuroimmunology

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Ž .Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis MS and experimental autoimmune Ž . encephalomyelitis EAE in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of Ž . marmoset monkeys Callithrix jacchus with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions Ž . Ž . may result from local CD40-CD40L interactions. CD40 ligand CD40L and B7-2 CD86 were also expressed, but to a lower extent, Ž . while B7-1 CD80 expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual Ž . lesions during active disease IFN-a, IFN-g , TNF-a, IL-1a , IL-1b, IL-2, IL-4, IL-10 and IL-12 . This suggests that relative levels rather than sequential expression of Th1-and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention. q

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Animal models of human disease Experimental autoimmune encephalomyelitis in rodents as a model for human demyelinating disease

Cited by 204 publications

References 88 publications

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Peroxisome Proliferator-Activated Receptor-γ Agonist 15-Deoxy-Δ12,1412,14-Prostaglandin J2 Ameliorates Experimental Autoimmune Encephalomyelitis

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus)

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